Differentiation status of rat ductal cells and ethionine-induced hepatic carcinomas defined with surface-reactive monoclonal antibodies.

To gain further insight into the differentiation of oval cells and their role in carcinogenesis, we have generated cell surface reactive monoclonal antibodies (MAbs) by a Balb/c nude mouse (nu/nu) immunization protocol. Three MAbs designated OC.4, OC.5, and OC.10 were generated from a mouse immunized with CDE6, an oval cell line established from oval cells induced by feeding a choline-deficient diet containing 0.1% ethionine (CDE). These MAbs demonstrated stage-specific expression in fetal liver and displayed strong reactivity with oval and bile duct epithelial cells. In general, oval cells displayed a more mature phenotype than fetal ductal cells, suggesting the existence in adult liver of more primitive ductal progenitors. A fourth MAb recognized a cytoplasmic antigen (OC.6) expressed by mucus-secreting hepatic ducts induced by CDE diet. Immunocytochemical analysis indicated that OC.4, OC.5, and OC.10 were also expressed on CDE-induced, OV6+ hepatocellular carcinomas (HCC) but not on OV6+ HCC induced by the Solt/Farber protocol. In most cases, CDE-induced, OV6+ HCC expressed early ductal developmental markers such as OC.10 but lacked those expressed at later stages (OC.5, OC.4). These new MAb will be useful for characterizing HCC subpopulations with oval cell characteristics and for isolating biliary cells at antigenically defined stages during differentiation. Copyright 2000 Academic Press.